István Márton Takács1, Beáta Szebeni1,2, Zoltán Varga3, Éva Pállinger4, Domonkos Pap1,2, Apor Veres-Székely1, Zoltán Kiss1,2, J. Attila Szabó1,2, S. György Reusz1, Ádám Vannay1,2
1 1st Department of Paediatrics, Semmelweis University, Budapest, Hungary
2 Pediatrics and Nephrology Research Group, MTA-SE, Budapest, Hungary
3 Biological Nanochemistry Research Group, MTA-TTK, Budapest, Hungary
4 Department of Genetics, Cell- and Immunobiology
Introduction and Aims: Extracellular vesicles (EVs) can protect against myocardial infarction, acute kidney injury or liver fibrosis. However, the impact of EVs derived from dialysis effluents (PDE) on the development of peritoneal fibrosis remained unclear. Our aim was to investigate this field.
Methods: PDE were collected from children receiving continuous ambulatory peritoneal dialysis (CAPD) treatment. PDE derived EVs were isolated by ultrafiltration and characterised by dynamic light scattering (DLS), Fourier transformation infrared spectroscopy and flow cytometry (FACS). Primer peritoneal fibroblasts (pPFs) were isolated from CAPD receiving patients. pPFs were treated with PDE derived EVs and their effect on their endogenous proliferation and platelet derived growth factor (PDGF) induced proliferation were measured by MTT test after 24h. Isolated EVs were intraperitoneally administered to a chlorhexidine gluconate (CG) induced C57BL/6 mice model of peritoneal fibrosis to measure the effects on submesothelial thickening.
Results: The average size of EVs was about 80 [40-150] nm. Lipid content and protein to lipid ratio was typical for EVs. FACS analysis demonstrated CD81 and annexin positivity. PDE derived EVs could enter into the cytoplasm of pPFs. Incubation of pPFs cells with PDE derived EVs significantly reduced endogenous and PDGF induced proliferation rate. PDE derived EVs could be detected in the peritoneal membrane of C57/BL6 mice and contributed to decreased submesothelial thickness.
Conclusion: PDE derived EVs significantly inhibit the PDGF induced proliferation of pPFs. The anti-proliferative effect of EVs may contribute to the preservation of the peritoneal membrane structure. However, future in vivo and in vitro experiments are required for testing the therapeutic potential in PD and their impact as potential biomarker.
This Project was supported by the ÚNKP-18-4-SE 109 and the ÚNKP-18-3-III-SE-29 New National Excellence Program of the Ministry of Human Capacities and the János Bolyai Research Scholarship of the Hungarian Academy of Sciences.
Doctoral School: Clinical Medicine PhD School
Program: Prevention of Chronic Diseases in Childhood
Supervisor: Sample Name Ádám Vannay
E-mail address: firstname.lastname@example.org